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Intellectual disability, autosomal recessive 6(MRT6)

MedGen UID:
370848
Concept ID:
C1970198
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 6; MRT6
 
Gene (location): GRIK2 (6q16.3)
 
Monarch Initiative: MONDO:0012614
OMIM®: 611092

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the GRIK2 gene. [from MONDO]

Clinical features

From HPO
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Kinetic tremor
MedGen UID:
1638576
Concept ID:
C4551521
Sign or Symptom
Tremor that occurs during any voluntary movement. It may include visually or non-visually guided movements. Tremor during target directed movement is called intention tremor.
Reduced social responsiveness
MedGen UID:
1841569
Concept ID:
C5826975
Finding
A reduced ability to participate in the back-and-forth flow of social interaction appropriate to culture and developmental level, which is normally characterized by an influence of the behavior of one person on the behavior of another person. This results in difficulty interacting with others through emotional, physical, or verbal communication.

Professional guidelines

PubMed

Langhammer F, Maroofian R, Badar R, Gregor A, Rochman M, Ratliff JB, Koopmans M, Herget T, Hempel M, Kortüm F, Heron D, Mignot C, Keren B, Brooks S, Botti C, Ben-Zeev B, Argilli E, Sherr EH, Gowda VK, Srinivasan VM, Bakhtiari S, Kruer MC, Salih MA, Kuechler A, Muller EA, Blocker K, Kuismin O, Park KL, Kochhar A, Brown K, Ramanathan S, Clark RD, Elgizouli M, Melikishvili G, Tabatadze N, Stark Z, Mirzaa GM, Ong J, Grasshoff U, Bevot A, von Wintzingerode L, Jamra RA, Hennig Y, Goldenberg P, Al Alam C, Charif M, Boulouiz R, Bellaoui M, Amrani R, Al Mutairi F, Tamim AM, Abdulwahab F, Alkuraya FS, Khouj EM, Alvi JR, Sultan T, Hashemi N, Karimiani EG, Ashrafzadeh F, Imannezhad S, Efthymiou S, Houlden H, Sticht H, Zweier C
Genet Med 2023 Aug;25(8):100885. Epub 2023 May 8 doi: 10.1016/j.gim.2023.100885. PMID: 37165955
Shang S, Mei Y, Wang T, Zheng X, Chen K, Xiong S, Dong Y, Chang Y, Wu X, Kong X, Tan M, Wu L, Zhang Y, Xiao Y, Xie Y, Cai G, Chen X, Li Q
Clin Nephrol 2022 Jun;97(6):328-338. doi: 10.5414/CN110476. PMID: 35142283
Salen G, Steiner RD
J Inherit Metab Dis 2017 Nov;40(6):771-781. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0093-8. PMID: 28980151

Recent clinical studies

Etiology

Pennings M, Meijer RPP, Gerrits M, Janssen J, Pfundt R, de Leeuw N, Gilissen C, Gardeitchik T, Schouten M, Voermans N, van de Warrenburg B, Kamsteeg EJ
Eur J Hum Genet 2023 Jun;31(6):654-662. Epub 2023 Feb 13 doi: 10.1038/s41431-023-01312-0. PMID: 36781956Free PMC Article
Putoux A, Alqahtani A, Pinson L, Paulussen AD, Michel J, Besson A, Mazoyer S, Borg I, Nampoothiri S, Vasiljevic A, Uwineza A, Boggio D, Champion F, de Die-Smulders CE, Gardeitchik T, van Putten WK, Perez MJ, Musizzano Y, Razavi F, Drunat S, Verloes A, Hennekam R, Guibaud L, Alix E, Sanlaville D, Lesca G, Edery P
Clin Genet 2016 Dec;90(6):550-555. Epub 2016 Jun 2 doi: 10.1111/cge.12781. PMID: 27040866
Matern D, He M, Berry SA, Rinaldo P, Whitley CB, Madsen PP, van Calcar SC, Lussky RC, Andresen BS, Wolff JA, Vockley J
Pediatrics 2003 Jul;112(1 Pt 1):74-8. doi: 10.1542/peds.112.1.74. PMID: 12837870
Hennekam RC, Stevens CA, Van de Kamp JJ
Am J Med Genet Suppl 1990;6:56-64. doi: 10.1002/ajmg.1320370610. PMID: 2118780
Rimoin DL
Birth Defects Orig Artic Ser 1971 May;7(6):12-20. PMID: 4375505

Diagnosis

Pennings M, Meijer RPP, Gerrits M, Janssen J, Pfundt R, de Leeuw N, Gilissen C, Gardeitchik T, Schouten M, Voermans N, van de Warrenburg B, Kamsteeg EJ
Eur J Hum Genet 2023 Jun;31(6):654-662. Epub 2023 Feb 13 doi: 10.1038/s41431-023-01312-0. PMID: 36781956Free PMC Article
Saleh S, Beyyumi E, Al Kaabi A, Hertecant J, Barakat D, Al Dhaheri NS, Al-Gazali L, Al Shamsi A
Clin Genet 2021 Nov;100(5):573-600. Epub 2021 Aug 19 doi: 10.1111/cge.14044. PMID: 34374989
Corona-Rivera JR, Zapata-Aldana E, Bobadilla-Morales L, Corona-Rivera A, Peña-Padilla C, Solis-Hernández E, Guzmán C, Richmond E, Zahl C, Zenker M, Sukalo M
Am J Med Genet A 2016 Jun;170(6):1495-501. Epub 2016 Mar 17 doi: 10.1002/ajmg.a.37630. PMID: 26989884
De Laey JJ
Bull Soc Belge Ophtalmol 1991;241:41-50. PMID: 1840995
Küster W, Majewski F
Eur J Pediatr 1986 Apr;144(6):574-8. doi: 10.1007/BF00496039. PMID: 3709570

Therapy

Buyukyilmaz G, Adiguzel KT, Kılıc E
Am J Med Genet A 2023 Jun;191(6):1581-1585. Epub 2023 Feb 23 doi: 10.1002/ajmg.a.63163. PMID: 36815763
Good AJ, Nielson CB, Schoch JJ
Pediatr Dermatol 2019 Nov;36(6):926-928. Epub 2019 Oct 6 doi: 10.1111/pde.13973. PMID: 31588604
Salen G, Steiner RD
J Inherit Metab Dis 2017 Nov;40(6):771-781. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0093-8. PMID: 28980151
Roques G, Munzer M, Barthez MA, Beaufils S, Beaupain B, Flood T, Keren B, Bellanné-Chantelot C, Donadieu J
Pediatr Blood Cancer 2014 Jun;61(6):1041-8. Epub 2014 Jan 30 doi: 10.1002/pbc.24964. PMID: 24482108
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948

Prognosis

Alkhater RA, Wang P, Ruggieri A, Israelian L, Walker S, Scherer SW, Smith ML, Minassian BA
Ann Clin Transl Neurol 2019 Apr;6(4):807-811. Epub 2019 Mar 7 doi: 10.1002/acn3.727. PMID: 31020005Free PMC Article
Nicolas E, Poitelon Y, Chouery E, Salem N, Levy N, Mégarbané A, Delague V
Eur J Hum Genet 2010 Oct;18(10):1107-13. Epub 2010 Jun 9 doi: 10.1038/ejhg.2010.82. PMID: 20531441Free PMC Article
Kerstjens-Frederikse WS, Brunner HG, van Dael CM, van Essen AJ
Am J Med Genet A 2005 May 1;134(4):450-3. doi: 10.1002/ajmg.a.30662. PMID: 15793834
Shashi V, Zunich J, Kelly TE, Fryburg JS
J Med Genet 1995 Jun;32(6):465-9. doi: 10.1136/jmg.32.6.465. PMID: 7666399Free PMC Article
Hennekam RC, Stevens CA, Van de Kamp JJ
Am J Med Genet Suppl 1990;6:56-64. doi: 10.1002/ajmg.1320370610. PMID: 2118780

Clinical prediction guides

Almannai M, Marafi D, Zaki MS, Maroofian R, Efthymiou S, Saadi NW, Filimban B, Dafsari HS, Rahman F, Maqbool S, Faqeih E, Al Mutairi F, Alsharhan H, Abdelaty O, Bin-Hasan S, Duan R, Noureldeen MM, Alqattan A, Houlden H, Hunter JV, Posey JE, Lupski JR, El-Hattab AW
Clin Genet 2024 Jun;105(6):620-629. Epub 2024 Feb 14 doi: 10.1111/cge.14492. PMID: 38356149Free PMC Article
Altıntaş M, Yıldırım M, Uçar Çİ, Köse E, Bektaş Ö, Teber S
Clin Neurol Neurosurg 2023 Jul;230:107772. Epub 2023 May 8 doi: 10.1016/j.clineuro.2023.107772. PMID: 37167844
Langhammer F, Maroofian R, Badar R, Gregor A, Rochman M, Ratliff JB, Koopmans M, Herget T, Hempel M, Kortüm F, Heron D, Mignot C, Keren B, Brooks S, Botti C, Ben-Zeev B, Argilli E, Sherr EH, Gowda VK, Srinivasan VM, Bakhtiari S, Kruer MC, Salih MA, Kuechler A, Muller EA, Blocker K, Kuismin O, Park KL, Kochhar A, Brown K, Ramanathan S, Clark RD, Elgizouli M, Melikishvili G, Tabatadze N, Stark Z, Mirzaa GM, Ong J, Grasshoff U, Bevot A, von Wintzingerode L, Jamra RA, Hennig Y, Goldenberg P, Al Alam C, Charif M, Boulouiz R, Bellaoui M, Amrani R, Al Mutairi F, Tamim AM, Abdulwahab F, Alkuraya FS, Khouj EM, Alvi JR, Sultan T, Hashemi N, Karimiani EG, Ashrafzadeh F, Imannezhad S, Efthymiou S, Houlden H, Sticht H, Zweier C
Genet Med 2023 Aug;25(8):100885. Epub 2023 May 8 doi: 10.1016/j.gim.2023.100885. PMID: 37165955
Roques G, Munzer M, Barthez MA, Beaufils S, Beaupain B, Flood T, Keren B, Bellanné-Chantelot C, Donadieu J
Pediatr Blood Cancer 2014 Jun;61(6):1041-8. Epub 2014 Jan 30 doi: 10.1002/pbc.24964. PMID: 24482108
Uyguner O, Kayserili H, Li Y, Karaman B, Nürnberg G, Hennies H, Becker C, Nürnberg P, Başaran S, Apak MY, Wollnik B
Clin Genet 2007 Mar;71(3):212-9. doi: 10.1111/j.1399-0004.2007.00762.x. PMID: 17309643

Recent systematic reviews

Kiaee F, Zaki-Dizaji M, Hafezi N, Almasi-Hashiani A, Hamedifar H, Sabzevari A, Shirkani A, Zian Z, Jadidi-Niaragh F, Aghamahdi F, Goudarzvand M, Yazdani R, Abolhassani H, Aghamohammadi A, Azizi G
Endocr Metab Immune Disord Drug Targets 2021;21(4):664-672. doi: 10.2174/1871530320666200613204426. PMID: 32533820

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